Based on studies that show (1) enterovirus 70 (E70) and Coxsackievirus A24 (CA24) can be grown in primary conjunctival cells of mice, rabbits, and/or monkeys and that E70 virus is replicating in rabbits, the following research program is proposed: (a) to attempt to infect the eyes and central nervous system of immature species of mice, rabbits, hamsters, and monkeys with virus isolates that grow well in cell or organ cultures of each particular species and to concentrate on determining the site and extensiveness of E70 replication in rabbits. (b) As suitable animal model systems are established, the effect of IF, IF inducers specific hyperimmune antibody, and temperature elevation on pathogenesis of this eye disease will be studied and explored in detail to determine optimal conditions for possible application of these defense factors for control of epidemics or individual cases of the disease. (c) To continue to determine from human specimens, including tears, eye scrapings, and acute and convalescent serum (a larger number of these specimens are present in the laboratory and more are expected) the relationships between antibody formaton virus replication and the pathogenesis of this infection in man. We expect to obtain more samples from patients, especially for those infected with E70. (d) To physically and biologically characterize and attempt to further clarify the role of the early appearing antiviral activity in tears on the pathogenesis of acute hemorrhagic conjunctivitis. (e) To continue the serum survey and to characterize the nature of the anti-E70 substance present in 90 percent of the serum samples. The presence of this substance complicates any serologic survey and could be a diagnostic problem during outbreaks when definitive diagnosis has to be accomplished serologically. It would be desirable to be able to easily eliminate this substance, if it is not antibody, prior to testing for specific antibody. (f) To explore in detail the synergistic antiviral effect of antibodies and interferon both in cell cultures and animal model systems.